The number of individuals annually affected by influenza virus continues to increase and with it the pressure of developing strategies to improve the efficacy and duration of vaccines. In the case of viral infections, antibody (Ab) production is often the mechanism of protection provided by the vaccine. However, activation of CD4* T cells is essential to mediate production of Ab by B cells durtng the initial immunization phase as well as during the protection phase. The generation of memory B cells is dependent on CD4'^ T cell help. The level of protection obtained with a vaccine is dependent on the strength of the primary Ab production against the vaccine. Thus, the administration of specific co-adjuvants that can boost Ab production during the influenza immunization could increase the efficacy and the protective effect of influenza vaccines. We show here that administration of IL-6 during the immunization with inactive influenza virus enhances anti-viral Ab response. We also show that the production of IL-21 by naive and memory CD4* T cells during in vivo and in vitro antigen stimulation is specifically induced by very low amounts of lL-6. Since IL-21 induces the differentiation of human and mouse naive and memory B cells into IgG-secreting plasma cells, and our recent data indicate that IL-21 is required for influenza virus Ab response, we propose that the administration of the innate cytokine IL-6 as a co-adjuvant during immunization enhances protection from viral infection indirectly by inducing IL-21 production in CD4* T cells, with IL-21 then promoting antiviral Ab production in B cells. We propose to demonstrate that 1) IL-6 promotes antibody production by B cells indirectly by inducing IL-21 production in CD4'' T cells, and IL-21 inducing plasma B cell generation, b) administration of lL-6 during immunization enhances protective antibody response to influenza virus, c) the effector CD4* T cells generated in the presence of IL-6 represent T follicular helper (Tfh) cells.